Liu Pei-Ying, Chang Dun-Cheng, Lo Yu-Sheng, Hsi Yi-Ting, Lin Chia-Chieh, Chuang Yi-Ching, Lin Shu-Hui, Hsieh Ming-Ju, Chen Mu-Kuan
Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, 500, Taiwan.
Cancer Research Center, Changhua Christian Hospital, Changhua, 500, Taiwan.
Environ Toxicol. 2018 Apr;33(4):446-453. doi: 10.1002/tox.22530. Epub 2018 Jan 10.
Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. The present study investigated the activity of osthole in suppressing NPC along with the underlying mechanism. Cell growth inhibition was measured using the MTT assay. Apoptosis was detected through 4',6-diamidino-2-phenylindole staining and flow cytometry. Western blotting was used to identify the signaling pathway. Osthole markedly inhibited cell proliferation and induced apoptosis in the NPC cell line. Western blotting results revealed the increased activation of caspases 3, 8, and 9 and poly (ADP-ribose) polymerase. Osthole treatment significantly reduced the expression of the antiapoptotic protein Bcl-2 and increased the expression of the proapoptotic proteins Bax, Bak, BimL, BimS, and t-Bid. Osthole treatment also increased the expression of Fas, FADD, TNF-R1, TNF-R2, DcR2, RIP, and DR5. In addition, osthole treatment significantly increased the expression levels of phosphorylated ERK1/2 and JNK1/2. These results suggested that osthole exerts cytotoxic effects on NPC cell lines mainly through apoptosis mediated by the Fas-Fas ligand and mitochondrial pathway. Osthole could be a potential anticancer agent for NPC.
鼻咽癌（NPC）在中国南方和东南亚地区呈地方性流行。本研究调查了蛇床子素抑制鼻咽癌的活性及其潜在机制。采用MTT法检测细胞生长抑制情况。通过4',6-二脒基-2-苯基吲哚染色和流式细胞术检测细胞凋亡。采用蛋白质免疫印迹法鉴定信号通路。蛇床子素显著抑制NPC细胞系的细胞增殖并诱导细胞凋亡。蛋白质免疫印迹结果显示，半胱天冬酶3、8和9以及聚（ADP-核糖）聚合酶的激活增加。蛇床子素处理显著降低抗凋亡蛋白Bcl-2的表达，并增加促凋亡蛋白Bax、Bak、BimL、BimS和t-Bid的表达。蛇床子素处理还增加了Fas、FADD、TNF-R1、TNF-R2、DcR2、RIP和DR5的表达。此外，蛇床子素处理显著增加了磷酸化ERK1/2和JNK1/2的表达水平。这些结果表明，蛇床子素主要通过Fas-Fas配体和线粒体途径介导的凋亡对NPC细胞系发挥细胞毒性作用。蛇床子素可能是一种潜在的鼻咽癌抗癌药物。
